Department of Mechanical Engineering, Division of Materials Science and Engineering, Boston University, Boston, MA 02215.
Photonics Center, Boston University, Boston, MA 02215.
Proc Natl Acad Sci U S A. 2020 May 19;117(20):10639-10644. doi: 10.1073/pnas.1922172117. Epub 2020 Apr 29.
The lack of rapid antibiotic susceptibility tests adversely affects the treatment of bacterial infections and contributes to increased prevalence of multidrug-resistant bacteria. Here, we describe an all-electrical approach that allows for ultrasensitive measurement of growth signals from only tens of bacteria in a microfluidic device. Our device is essentially a set of microfluidic channels, each with a nanoconstriction at one end and cross-sectional dimensions close to that of a single bacterium. Flowing a liquid bacteria sample (e.g., urine) through the microchannels rapidly traps the bacteria in the device, allowing for subsequent incubation in drugs. We measure the electrical resistance of the microchannels, which increases (or decreases) in proportion to the number of bacteria in the microchannels. The method and device allow for rapid antibiotic susceptibility tests in about 2 h. Further, the short-time fluctuations in the electrical resistance during an antibiotic susceptibility test are correlated with the morphological changes of bacteria caused by the antibiotic. In contrast to other electrical approaches, the underlying geometric blockage effect provides a robust and sensitive signal, which is straightforward to interpret without electrical models. The approach also obviates the need for a high-resolution microscope and other complex equipment, making it potentially usable in resource-limited settings.
缺乏快速抗生素药敏试验会对细菌感染的治疗产生不利影响,并导致多药耐药菌的流行率增加。在这里,我们描述了一种全电化方法,该方法允许在微流控设备中仅对数十个细菌进行超灵敏的生长信号测量。我们的设备本质上是一组微流道,每个微流道的一端都有一个纳米缩口,其横截面尺寸接近于单个细菌。将液体细菌样品(例如尿液)流过微通道可迅速将细菌捕获在设备中,随后可在药物中孵育。我们测量微通道的电阻,其与微通道中的细菌数量成正比地增加(或减少)。该方法和设备可在大约 2 小时内进行快速抗生素药敏试验。此外,抗生素药敏试验过程中电阻的短时间波动与抗生素引起的细菌形态变化相关。与其他电化方法相比,基本的几何阻塞效应提供了一个稳健且灵敏的信号,无需电模型即可直接解释。该方法还省去了高分辨率显微镜和其他复杂设备的需求,使其在资源有限的环境中具有潜在的使用价值。